Respiration sensor processing for phrenic nerve activation detection

ABSTRACT

An implantable cardiac device includes a sensor for sensing patient respiration and detecting phrenic nerve activation. A first filter channel attenuates first frequencies of the sensor signal to produce a first filtered output. A second filter channel attenuates second frequencies of the respiration signal to produce a second filtered output. Patient activity is evaluated using the first filtered output and phrenic nerve activation caused by cardiac pacing is detected using the second filtered output.

RELATED APPLICATIONS

This application claims the benefit of Provisional Patent ApplicationSer. No. 61/181,658, filed on May 27, 2009, to which priority is claimedpursuant to 35 U.S.C. §119(e) and which is hereby incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates generally to cardiac devices and methods,and, more particularly, to characterization of phrenic nerve activationand phrenic nerve activation avoidance during cardiac electricaltherapy.

BACKGROUND OF THE INVENTION

When functioning normally, the heart produces rhythmic contractions andis capable of pumping blood throughout the body. The heart hasspecialized conduction pathways in both the atria and the ventriclesthat enable excitation impulses (i.e. depolarizations) initiated fromthe sino-atrial (SA) node to be rapidly conducted throughout themyocardium. These specialized conduction pathways conduct thedepolarizations from the SA node to the atrial myocardium, to theatrio-ventricular node, and to the ventricular myocardium to produce acoordinated contraction of both atria and both ventricles.

The conduction pathways synchronize the contractions of the musclefibers of each chamber as well as the contraction of each atrium orventricle with the opposite atrium or ventricle. Without thesynchronization afforded by the normally functioning specializedconduction pathways, the heart's pumping efficiency is greatlydiminished. Patients who exhibit pathology of these conduction pathwayscan suffer compromised cardiac output.

Cardiac rhythm management (CRM) devices have been developed that providepacing stimulation to one or more heart chambers in an attempt toimprove the rhythm and coordination of atrial and/or ventricularcontractions. CRM devices typically include circuitry to sense signalsfrom the heart and a pulse generator for providing electricalstimulation to the heart. Leads extending into the patient's heartchamber and/or into veins of the heart are coupled to electrodes thatsense the heart's electrical signals and deliver stimulation to theheart in accordance with various therapies for treating cardiacarrhythmias and dyssynchrony.

Pacemakers are CRM devices that deliver a series of low energy pacepulses timed to assist the heart in producing a contractile rhythm thatmaintains cardiac pumping efficiency. Pace pulses may be intermittent orcontinuous, depending on the needs of the patient. There exist a numberof categories of pacemaker devices, with various modes for sensing andpacing one or more heart chambers.

A pace pulse must exceed a minimum energy value, or capture threshold,to “capture” the heart tissue, generating an evoked response thatgenerates a propagating depolarization wave that results in acontraction of the heart chamber. If a pace pulse energy is too low, thepace pulses may not reliably produce a contractile response in the heartchamber and may result in ineffective pacing that does not improvecardiac function or cardiac output.

Pacing pulses can unintentionally stimulate nerves or muscles, even ifthe pulse energy is not sufficient to capture cardiac tissue. Forexample, a delivered pacing pulse may stimulate a patient's phrenicnerve, which runs proximate to the heart and innervates the diaphragm.The present invention provides methods and systems using phrenic nerveto detect phrenic nerve activation and avoid phrenic nerve activationduring cardiac pacing therapy.

SUMMARY OF THE INVENTION

The present invention involves approaches for sensing phrenic nerveactivation in conjunction with sensing patient activity and/or metabolicdemand. Some embodiments involve an implantable medical device includinga pulse generator configured to deliver cardiac pacing to a heart. Animpedance sensor generates a signal modulated by patient respiration,the sensor signal available at a sensor output terminal. A first filterchannel is coupled to the sensor output and attenuates first frequenciesof the sensor signal to produce a first filtered output. A second filterchannel, separate from the first filter channel, is coupled to thesensor output. The second filter channel attenuates second frequenciesof the sensor signal to produce a second filtered output. The medicaldevice includes circuitry configured to evaluate patient respirationusing the first filtered output and to detect phrenic nerve activationcaused by cardiac pacing using the second filtered output.

In some implementations, the second filter channel comprises a notchfilter. For example, the filter characteristics of the notch filter canbe dynamically alterable based on cardiac rate.

In some implementations, the second filter channel comprises a high passfilter having a low frequency cut off of about 5 Hz.

According to one aspect of the invention, analog circuitry is coupledbetween the sensor output and the first and second filter channels andthe second filter channel includes a filter circuit that issubstantially matched to an impulse response of the analog circuitry.For example, the filter circuit can substantially attenuate frequenciesother than the impulse response frequencies of the analog circuitry. Thecharacteristics of the filter circuitry may be individually mapped tothe impulse response during device testing.

In some implementations, the circuitry includes a timer configured totime a phrenic nerve activation detection interval which is startedfollowing delivery of a pacing pulse to a cardiac chamber and is stoppedbefore delivery of a subsequent pacing pulse to the cardiac chamber. Thecircuitry is configured to sensor for phrenic nerve activation duringthe phrenic nerve detection interval.

In some implementations, the device also includes pacing controlcircuitry configured to adapt a cardiac pacing rate based on evaluationof the patient respiration.

The medical device may also include a second sensor configured toproduce a sensor signal, wherein the circuitry is configured to use boththe sensor signal and the second filtered output to detect the phrenicnerve activation.

According to additional aspects of the invention, the medical device mayinclude an accelerometer configured to generate a signal modulated byacceleration that is available at an accelerometer output terminal. Athird filter channel is coupled to the accelerometer output terminal andis configured to attenuate third frequencies of the accelerometer signalto produce a third filtered output. A fourth filter channel is coupledto the accelerometer output, and is separate from the third filterchannel. The fourth filter channel is configured to attenuate fourthfrequencies of the accelerometer signal to produce a fourth filteredoutput, wherein the circuitry is configured to detect the phrenic nerveactivation using the second filtered output and the fourth filteredoutput.

The circuitry may develop a sensor indicated pacing rate based on one orboth of the first filtered output and the third filtered output.

According to some aspects, the circuitry may be configured to use thefirst filtered output to determine respiration phase and to use thesecond filtered output to detect the phrenic nerve activation inconjunction with the respiration phase.

Yet another embodiment of the invention is directed to a method ofoperating an implantable medical device. Patient respiration is sensedand a sensor signal modulated by patient respiration is generated at asensor output terminal. The sensor signal is processed through separatesignal processing channels, including a first signal processing channelhaving first signal processing characteristics and a second signalprocessing channel having second signal processing characteristics.Patient respiration is evaluated using an output of the first signalprocessing channel. Phrenic nerve activation caused by cardiac pacing isdetected using an output of the second signal processing channel.

For example, the first signal processing channel may include firstfilter circuitry and the first signal processing characteristics areconfigured to attenuate a first set of frequencies from the sensorsignal. The second signal processing channel may include second filtercircuitry and the second signal processing characteristics areconfigured to attenuate a second set of frequencies from the sensorsignal.

According to some implementations, the second signal processing channelcomprises a notch filter having characteristics that are adaptable basedon cardiac rate.

According to some implementations the second signal processingcharacteristics comprise a low frequency cut off that substantiallyattenuates respiration components and cardiac components from the outputof the second signal processing channel.

Another aspect of the invention involves starting a phrenic nerveactivation detection interval upon or after delivery of a cardiac paceduring a cardiac cycle. The phrenic nerve detection interval is endedduring the cardiac cycle and sensing for the phrenic nerve activationoccurs during the phrenic nerve detection interval.

Determining the phrenic nerve activation may involve determining atransition zone for phrenic nerve activation. The cardiac pacing energymay be set to be above the cardiac capture threshold and below atransition zone threshold for phrenic nerve activation.

According to certain implementations, switching from one cardiac pacingelectrode configuration to another cardiac pacing electrodeconfiguration may occur based on detection of the phrenic nervestimulation.

The above summary of the present invention is not intended to describeeach embodiment or every implementation of the present invention.Advantages and attainments, together with a more complete understandingof the invention, will become apparent and appreciated by referring tothe following detailed description and claims taken in conjunction withthe accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flowchart illustrating a method of characterizing phrenicnerve activation relative to respiration in accordance with variousembodiments of this disclosure;

FIG. 2 is a graph illustrating respiration phases in accordance withembodiments of this disclosure;

FIGS. 3-4 illustrate accelerometer data plots in accordance withembodiments of this disclosure;

FIG. 5 is a multi-trace graph showing electrical cardiac, accelerometer,and impedance data collected during pulse delivery in accordance withembodiments of this disclosure;

FIG. 6 is a flowchart illustrating a method of characterizing phrenicnerve activation in accordance with embodiments of this disclosure;

FIG. 7 is a flowchart illustrating a method of characterizing phrenicnerve activation in accordance with embodiments of this disclosure;

FIG. 8 is a graph illustrating various aspects of strength-durationpacing pulse parameters and a transition zone in accordance withembodiments of this disclosure;

FIG. 9 is a block diagram of a system incorporating phrenic nerveactivation characterization and avoidance circuitry in accordance withembodiments of this disclosure;

FIG. 10 is a diagram illustrating a patient-internal device inaccordance with embodiments of this disclosure;

FIG. 11A is a block diagram of medical device circuitry configured toprocess a sensor signal output using separate signal processing channelsfor activity/metabolic demand sensing and phrenic nerve activationsensing in accordance with embodiments of this disclosure;

FIG. 11B is a block diagram of medical device circuitry having a singlesignal processing channel configured to implement time-multiplexedsignal processing functions in accordance with embodiments of thisdisclosure;

FIG. 12 illustrates the output of an accelerometer before and afterprocessing by two different signal processing circuits;

FIG. 13 depicts three graphs representing a thoracic impedance signalthat is produced using different three sets of signal processingcharacteristics;

FIGS. 14A-14C are block diagrams of medical devices configured to detectphrenic nerve activation and to use blended sensor outputs for rateadaptation in accordance with embodiments of this disclosure;

FIG. 15 is a flow diagram illustrating processes implementable in acardiac device for detecting phrenic nerve activation using a phrenicnerve activation detection interval in accordance with embodiments ofthis disclosure;

FIG. 16 is a flow diagram illustrating various optional processes forphrenic nerve activation detection in conjunction with respiration ratesensing in accordance with embodiments of this disclosure; and

FIGS. 17A-B depict a flow diagram illustrating an algorithm for cardiaccapture threshold testing that also includes a process for ensuring thatthe pacing voltage selected based on the cardiac capture threshold doesnot produce phrenic nerve activation in accordance with embodiments ofthis disclosure.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings forming a part hereof, and inwhich are shown by way of illustration, various embodiments by which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

Systems, devices, or methods according to the present invention mayinclude one or more of the features, structures, methods, orcombinations thereof described herein. For example, a device or systemmay be implemented to include one or more of the advantageous featuresand/or processes described below in various different embodiments. It isintended that such a device or system need not include all of thefeatures described herein, but may be implemented to include selectedfeatures that provide for useful structures and/or functionality. Such adevice or system may be implemented to provide a variety of therapeuticor diagnostic functions.

A wide variety of implantable cardiac monitoring and/or stimulationdevices may be configured to implement phrenic nerve activationdetection algorithms of the present invention. A non-limiting,representative list of such devices includes cardiac monitors,pacemakers, cardiovertors, defibrillators, resynchronizers, and othercardiac monitoring and therapy delivery devices. These devices may beconfigured with a variety of electrode arrangements, includingtransveneous, endocardial, and epicardial electrodes (i.e.,intrathoracic electrodes), and/or subcutaneous, non-intrathoracicelectrodes, including can, header, and indifferent electrodes, andsubcutaneous array(s) or lead electrodes (i.e., non-intrathoracicelectrodes).

In multi-electrode pacing systems, multiple pacing electrodes may bedisposed in a single heart chamber, in multiple heart chambers, and/orelsewhere in a patient's body. Electrodes used for delivery of pacingpulses may include one or more cathode electrodes and one or more anodeelectrodes. Pacing pulses are delivered via the cathode/anode electrodecombinations, where the term “electrode combination” denotes that atleast one cathode electrode and at least one anode electrode are used.An electrode combination may involve more than two electrodes, such aswhen multiple electrodes that are electrically connected are used as theanode and/or multiple electrodes that are electrically connected areused as the cathode.

Typically, pacing energy is delivered to the heart tissue via thecathode electrode(s) at one or more pacing sites, with a return pathprovided via the anode electrode(s). If cardiac capture occurs, theenergy injected at the cathode electrode site creates a propagatingwavefront of depolarization which may combine with other depolarizationwavefronts to trigger a contraction of the cardiac muscle. The cathodeand anode electrode combination that delivers the pacing energy definesthe pacing vector used for pacing.

Pacing pulses may be applied through multiple electrodes (i.e., pacingvectors defined by various electrode combinations) in a single cardiacchamber in a timed sequence during the cardiac cycle to improvecontractility and enhance the pumping action of the heart chamber. It isgenerally desirable for each pacing pulse delivered via the multipleelectrode combinations to capture the cardiac tissue proximate to thecathode electrode. Capture of cardiac tissue depends upon, among otherthings, the vector used to deliver the pulse and various pulseparameters, such as the amplitude and duration of the pulse.

A cardiac capture threshold can be determined using, among othermethods, a step-down technique where a capture threshold is identifiedwhen loss of cardiac capture is detected after successive pacing cycles.A step-up technique can also be used, whereby a cardiac capturethreshold is identified when cardiac capture is first detected aftersuccessive pacing cycles without cardiac capture. Cardiac capture can bedetected using characteristics of an electrical cardiac signalindicating an intended cardiac response (e.g., a QRS complex).

Cardiac capture detection allows the cardiac rhythm management system toadjust the energy level of pace pulses to correspond to the optimumenergy expenditure that reliably produces a contraction. Further,cardiac capture detection allows the cardiac rhythm management system toinitiate a back-up pulse at a higher energy level whenever a pace pulsedoes not produce a contraction.

Stimulation characteristics of a cardiac pacing therapy are dependent onmany factors, including the distance between the electrodes, proximityto targeted cardiac tissue, proximity to non-targeted tissue susceptibleto unintended activation, type of tissue contacting and between theelectrodes, impedance between the electrodes, resistance between theelectrodes, and electrode type, among other factors. Such factors caninfluence the cardiac capture thresholds, as well as a patient's phrenicnerve activation thresholds. Stimulation characteristics can vary withphysiologic changes, electrode migration, patient position, physicalactivity level, body fluid chemistry, hydration, and disease state,among other factors. Therefore, the stimulation characteristics for eachelectrode combination are unique and can change over time. As such, itcan be useful to periodically determine the stimulation characteristicsfor each electrode combination for optimum pacing that avoidsundesirable tissue activation.

Bi-ventricular pacing provides therapy options for patients sufferingfrom heart failure. However, new challenges have been presented byplacement of the left-ventricular lead via the coronary sinus inbi-ventricular pacing systems. Due to the proximity of the coronaryveins to the phrenic nerve, left ventricular pacing may result inundesirable phrenic nerve stimulation. The phrenic nerve innervates thediaphragm, so unintended activation of the phrenic nerve can cause apatient to experience rapid contraction of the diaphragm, similar to ahiccup. Unintended activation of the phrenic nerve via a cardiac pacingpulse can be uncomfortable for the patient, and can interfere withbreathing. Therefore, phrenic nerve activation from cardiac pacing maycause the patient to exhibit uncomfortable breathing patterns timed withthe left-ventricular pace.

A phrenic nerve activation threshold for a pacing parameter (e.g.,voltage, duration) for a particular electrode combination, above whichthe phrenic nerve will be activated by a pacing pulse, can bedetermined. One method for determining a phrenic nerve activationthreshold includes sensing for some signature of phrenic nerveactivation timed with the delivery of pacing pulses. If no change inphrenic nerve activation is sensed (e.g., is not lost or gained) usingthe level of electrical energy delivered, the energy level can beiteratively changed (e.g., decreased in a step down test or increased ina step up test) for subsequent trials of delivering electrical energyand monitoring for phrenic nerve activation until phrenic nerveactivation is first lost (in the case of step-down scanning) or firstdetected (in the case of step-up scanning). The electrical energy levelat which phrenic nerve activation is first detected or first lost can bethe phrenic nerve activation threshold for the electrode combinationtested. The energy delivered during such a scan could also be used tosimultaneously perform other tests, such as searching for a cardiaccapture threshold.

Methods for evaluating phrenic nerve activation that may be incorporatedin embodiments of the present disclosure are disclosed in U.S. Pat. Nos.6,772,008 and 7,392,086, each of which are herein incorporated byreference in their respective entireties.

Programming a pacing device to avoid undesirable stimulation, such asphrenic nerve activation, is not one dimensional, as many other factorscan be important in setting appropriate pacing parameters. For example,a pace pulse must exceed a minimum energy value, or capture threshold,to produce an intended contraction of cardiac tissue. It is desirablefor a pace pulse to have sufficient energy to stimulate capture of theheart without expending energy significantly in excess of the capturethreshold. Thus, proper characterization of the various tissueactivation thresholds provides efficient pace energy management. If thepace pulse energy is too low, the pace pulses may not reliably produce acontractile response in the heart and may result in ineffective pacing.

Another complication in determining appropriate pacing pulse parametersconcerns seemingly erratic phrenic activation behavior even when pacingparameters are held constant. For example, in a step down test it ispossible to lower cardiac pacing pulse voltage until phrenic nerveactivation is not detected, and if the pacing parameters are heldconstant subsequent pacing parameters may not cause phrenic nerveactivation. However, in some cases, the subsequent pacing pulses willcause phrenic nerve activation despite the same pacing parameters notcausing phrenic nerve activation in one or more previous pulses.

The inventors have investigated this phenomenon and have linked thephases of respiration during which pacing pulses are delivered toincreased and decreased susceptibility to phrenic nerve activation. Forexample, some subjects are more susceptible to phrenic nerve activationwhen the subjects are inhaling relative to other portions of therespiratory cycle, such as exhalation. Some subjects are moresusceptible to phrenic nerve activation when they are at the deepestpart of their breaths (at the point of maximum inhalation) relative toother portions of the respiratory cycle. Some subjects are lesssusceptible to phrenic nerve activation when the subject is exhaling orbetween breaths (e.g., not inhaling or exhaling) relative to otherportions of the respiratory cycle. The particular susceptible phase fora particular patient may be influenced by the chosen pacing vector forpacing pulse delivery, or other pacing parameters, and could changechronically. The present disclosure concerns methods and systems forcharacterizing a patient's phrenic nerve activation response relative torespiration cycle and determining pacing parameters based on thecharacterization, among other things.

The cardiac pace pulse parameter range within which phrenic nerveactivation is dependent on respiration phase is herein referred to asthe transition zone. The transition zone corresponds to the pulseparameter range within which a cardiac pacing pulse will reliably (e.g.,always) cause phrenic nerve activation above an upper boundary and willnot cause phrenic nerve activation below a lower boundary, and betweenthe upper and lower boundaries will sometimes cause phrenic nerveactivation dependent on respiration cycle phase.

For example, if the cardiac pacing pulse parameter is voltage, then atransition zone can be the voltage range within which the respiratoryphase influences whether a pulse having a voltage within the rangecauses phrenic nerve activation. Above the transition zone (e.g.,voltages greater than the upper transition zone boundary), essentiallyall pulses will activate the phrenic nerve and below the transition zone(e.g., voltages less than the lower transition zone boundary)essentially no pulses will activate the phrenic nerve. Within thetransition zone (e.g., voltage less than the upper transition zoneboundary and greater than the lower transition zone boundary), any pulsehaving constant output parameters may or may not cause phrenic nerveactivation, with phrenic nerve activation depending on the phase of therespiration cycle when the pulse was delivered. Different electrodecombinations can have different thresholds and transitions zone ranges.

FIG. 1 illustrates a method 100 for characterizing a patient's phrenicnerve activation response relative to respiration. The method 100includes monitoring 110 a patient's respiration using an impedancesignal.

FIG. 2 illustrates an impedance signal 200 that can be used in themethod 100 of FIG. 1, as well in the other embodiments discussed herein.The impedance signal 200 is proportional to the transthoracic impedanceillustrated as impedance 201 on the abscissa of the left side of thegraph. The impedance 201 increases during any respiratory inspirationand decreases during any respiratory expiration. The impedance signal200 is also proportional to the amount of air inhaled, denoted the tidalvolume 202, illustrated on the abscissa of the right side of the graph.

The method 100 of FIG. 1 further includes identifying 120 at least oneof inhalation, peak inhalation, and exhalation phases of the patientrespiration based on the monitored 110 impedance signal. In someembodiments, all of these phases will be identified 120, and in someother embodiments only certain phases will be identified 120, such asinspiration and expiration.

A respiration cycle can be divided into an inspiration periodcorresponding to the patient inhaling, an expiration periodcorresponding to the patient exhaling, peak inhalation corresponding tothe period after inhalation before exhalation, and a non-breathingperiod occurring after exhalation and before the next inhalation.Respiration phases can be established using an inspiration threshold 210and an expiration threshold 220. The inspiration threshold 210 marks thebeginning of an inspiration period 230 and is determined by thetransthoracic impedance signal 200 rising above the inspirationthreshold 210. The inspiration period 230 ends when the transthoracicimpedance signal 200 is at maximum 240. The maximum transthoracicimpedance signal 240 corresponds to both the end of the inspirationinterval 230 and the beginning of an expiration interval 250. Theexpiration interval 250 continues until the transthoracic impedance 200falls below an expiration threshold 220. A non-breathing interval 260starts from the end of the expiration period 250 and continues until thebeginning of a next inspiration period 270.

Taking the derivative of the impedance signal 200 can also identifyrespiratory phases. For example, the time 203 during which thederivative value of the impedance signal 200 is positive can correspondto the inspiration phase 230. The time 203 during which the derivativevalue of the impedance signal 200 is negative can correspond to theexpiration phase 230. The time 203 during which the derivative value ofthe impedance signal 200 turns zero after being positive (inspiration)can correspond to the peak inspiration phase 241. A non-breathing phase260 can be identified without use of a derivative as the time 203 duringwhich the impedance signal 200 is below the expiration threshold 220.

The method 100 further includes delivering 130 one or more cardiacpacing pulses coinciding with one or more of the respiratory phases. Forexample, cardiac pacing pulses from a left ventricular lead electrodecan be timed to be delivered within each of the respiration phasesdiscussed herein, including during inspiration, peak inspiration,expiration, and non-breathing (peak expiration) phases.

The method 100 can then determine 140 whether the patient's phrenicnerve was stimulated by any of the pacing pulses using an accelerometersignal. Such a method can be used to determine if the cardiac pacingpulse parameters are associated with phrenic stimulation during one ormore phases of respiration. Such techniques can also indicate if apatient is more susceptible to phrenic nerve activation duringparticular respiratory phases, by tracking during which phase or phasesof respiration pulse delivery was correlated with phrenic nerveactivation.

In method 100, as well as in the others discussed herein, it can beuseful to hold cardiac pacing pulse parameters constant (e.g., constantvoltage, duration, vector etc.) so that the timing of the pulses duringthe various respiration phases can be isolated as a variable. Forexample, pulses having particular voltage and duration parameters can bedelivered during inspiration, peak inspiration, and expiration phases todetermine whether respiratory phase plays a role in whether the phrenicnerve is stimulated using the parameter settings. One or more of theparameters can then be iteratively changed and tested to determine atwhich parameter settings the respiratory cycle influences phrenic nerveactivation, and which cardiac pace pulse energy parameter settings arenot associated with phrenic nerve activation during any phase ofrespiration.

A goal of various embodiments concerns finding cardiac pacing pulseparameter settings or ranges of settings that are not associated withphrenic nerve stimulation during any respiratory phase. Such settingscan include pulse voltage, duration, and vector. Therefore, in variousembodiments, different (and typically lower power) pacing pulseparameter settings are sought if any of the pulses delivered 130 duringthe various respiration phases were determined 140 to activate thepatient's phrenic nerve. The method 100 can then be repeated untilcardiac pacing pulse parameter settings are found that do not stimulatethe patient's phrenic nerve during any of the respiratory phases.

The diaphragmatic response due to phrenic nerve stimulation can bedetected using an accelerometer signal or other vibration detectionmethods. An accelerometer can measure accelerations of the sensor inone, two, or three dimensions. Accelerometers are sensitive sufficientto output a signal indicating the quick, hiccup-like chest movementexperienced during phrenic nerve activation.

FIGS. 3-4 illustrate overlayed accelerometer signals (XL), measured inunits of gravity 310. The accelerometer signals 300 of FIG. 3 arerelatively flat and illustrate periods with no phrenic nerve activationvia cardiac pacing pulse. As such, FIG. 3 shows very little deviation inthe gravity signal 310 magnitude.

FIG. 4 shows accelerometer signals 400. Signals 400 have been overlayedto show a signature acceleration patterns of phrenic nerve activation asmeasured in gravity 410. In this example, acceleration associated withphrenic nerve activation is characterized by peaks 401 and 403.

Accelerometer signals could be evaluated in various ways to identifyphrenic nerve activation. For example, a detection window can beinitiated based on delivery 130 of a left ventricular pace pulse duringa respiration phase of interest, the detection window focusing onaccelerometer data. Such a window could open at the moment of pulsedelivery or after a period of time after pulse delivery, such as aperiod of time that is slightly less than the estimated or tested amountof time for a pulse to cause diaphragmic motion perceivable by a sensorfollowing delivery of the pulse. Other times to open a detection windoware also contemplated. Such a detection window can have a length(measured in time, such as milliseconds) and satisfaction criteria(e.g., characteristics of the data indicative of phrenic nerveactivation) that if met within the window indicate phrenic nerveactivation by the cardiac pacing pulse. For example, if one or morepeaks (e.g., peaks 401 and 403) are sensed within the window thenphrenic nerve activation associated with the left ventricular pulse canbe identified. Peaks and other features of accelerometer signalsassociated with phrenic nerve activation can be identified by timing,energy, and frequency-based methods or morphology analysis, for example.Limited duration of the window (e.g., a time between opening and closingof the window following pulse delivery) can focus collection of dataassociated with delivery of the cardiac pacing pulse for the amount oftime needed to collect the necessary amount of data for phrenic nerveactivation detection. In some embodiments, detection of phrenic nerveactivation is not limited to windows, but particular techniques and/orheightened sensitivity for the detection of phrenic nerve activation areused within the windows. The opening of detection windows based ondelivery of a left ventricular pace pulse to aid in detection of phrenicnerve activation associated with the left ventricular pace pulse can beperformed in any embodiment discussed herein, including FIGS. 1-10.

FIG. 5 represents a time 505 alignment of right ventricular electricalcardiac signal 501, left ventricular electrical cardiac signal 502,accelerometer signal 503, and impendence signal 504. Cardiac pace pulses551-564 are periodically delivered and associated cardiac activity(e.g., events 510, 520, 530) appears on the cardiac traces. The pulsevoltage parameter 509 is increased between some of the pace pulses551-564 from an initial 1.9 volts to 2.1 volts. Despite this continualpacing (increasing in voltage), continual phrenic nerve activation isnot detected. Rather, the accelerometer signal 503 indicates that theoccurrence of phrenic nerve activation is intermittent, and dependent onthe respiratory phase in which the particular pulses 551-564 weredelivered.

For example, the accelerometer signal 503 signatures 521 and 531indicate that the phrenic nerve was stimulated by evidence of thecharacteristic phrenic nerve activation patterns discussed herein. Thesephrenic nerve activation accelerometer signal 503 signatures 521 and 531immediately follow delivery of pulses 554 and 563 during inspirationphases 522 and 532 as indicated by the impedance signal 504. It is notedthat for this particular subject, pulse 552 delivered during anon-breathing period, pulse 555 delivered during expiration, and pulse564 delivered during peak inspiration, did not trigger phrenic nerveactivation. As such, methods of the present disclosure indicate thatthis particular subject is particularly susceptible to phrenic nerveactivation during inspiration periods relative to other respirationphases. Also, methods of the present disclosure indicate that thisparticular subject has a transition zone between at least 1.9 to 2.1volts because phrenic nerve activation between these voltages isdependent on respiration phase.

Without wishing to be bound by any particular theory, one possiblereason why phrenic nerve activation may be respiratory phase dependentfor a subject is that the dimensions between the pacing electrodes andthe phrenic nerve may change during the respiratory cycle, therebychanging the tissue through which the current flows. For example, as aparticular patient inhales the current path between pacing electrodesmay be more likely to traverse an area proximate the phrenic nerve, suchthat the patient is more susceptible to phrenic nerve activation duringinhalation.

FIG. 6 illustrates a method 600 for finding cardiac therapy pulseparameter settings that avoid phrenic nerve activation. The method 600can be initiated periodically on a preprogrammed schedule (e.g., oncedaily, weekly, or monthly, etc.), in response to detection of an event(e.g., sensing phrenic nerve activation, capture loss, and/or electrodecombination reconfiguring), as part of an automatic ventricularthreshold test, and/or by reception of a command (e.g., an input by adoctor or patient requesting automatic testing).

In some embodiments, one or more pacing parameters (e.g., pulse voltage,duration) will need to be set when the method 600 is initiated. Thepacing parameter could be set at a previously used pacing value (e.g.,when phrenic nerve activation was unexpectedly sensed), above apreviously used value, a default value, or programmed by a physician. Inthe case of a step-up test, it can be preferable to have the pacingparameter initially set at a relatively low setting, below which it isthought that phrenic nerve activation is unlikely. In the case of astep-down test, it can be preferable to have the pacing parameterinitially set at a relatively high setting at which it is thoughtphrenic nerve activation is likely. The method 600 is directed to astep-down test. However, the steps of the method 600 could be adaptedand used in a step-up test.

The method 600 includes monitoring 610 phases of patient respiration.Monitoring 610 can be performed using various techniques that canidentify respiratory phases, such as by collecting an impedance signalin the manner of FIG. 2. Cardiac pacing pulses can be delivered 620according to a cardiac pacing schedule concurrent or interspaced withmonitoring 610. During and/or after delivery 620 of each cardiac pacingpulse, phrenic nerve activation is monitored 630, such that activationof the phrenic nerve by any of the delivered 620 cardiac pacing pulsesis identified. Monitoring 630 for phrenic nerve activation can be doneby any technique for identifying phrenic nerve stimulation, such as byusing an accelerometer in the manner of FIGS. 3-5. Phrenic nerveactivation can also be sensed using an impedance sensor, which may showan abrupt disruption in the impedance signal breathing pattern if thephrenic nerve is activated (e.g., such as an abrupt disruption in therhythmic breathing patterns of the impedance signal 200 in FIG. 2).

After delivery 620 of each pulse, or at other times (e.g., every minute,after delivery 620 of every 10 pulses, or after each respiratory phaseor cycle), it is determined whether at least one pulse has beendelivered during each respiratory phase of interest 640. It is notedthat step 640, as well as the other techniques described herein, referto pulse delivery in an occurrence of a phase of interest, not in eachoccurrence of each phase of interest. For example, if the respiratoryphase of interest is inspiration, then 5 cycles of breathings will have5 instances of inspiration. The methods described herein do no need todeliver (e.g., 620) cardiac pacing pulses in each of the 5 instances ofinspiration. Rather, the methods can be completed by delivering theprescribed number of pacing pulses in the respiratory phase of interest(inspiration) over the course of many cycles (e.g., 100 cycles). In thisway, during some breathing cycles only cardiac support pacing isdelivered and none of the pace pulses are intended as testing forphrenic nerve activation. Continuing with the example above, in may bethat only 1 cardiac pacing pulse is delivered during inspiration overthe course of the 5 breath cycles. In some cases, cardiac pacing pulsesare delivered during several of the 5 inspiration phases, but only 1 ofthem is part of the test for phrenic nerve activation, wherein anaccelerometer signal is analyzed for phrenic nerve stimulation only inassociation with this 1 test pulse. In some embodiments, a detectionwindow is opened only in response to a pacing pulse that is consideredto be part of the test.

In some embodiments, all respiratory cycle phases are of interest, suchthat at least one pulse will need to be delivered 620 in each ofinspiration, peak inspiration, expiration, and non-breathing phases tosatisfy step 640 for a certain number of occurrences of these phases.However, in some other embodiments, not all respiration cycle phaseswill be of interest. For example, in some embodiments only inspirationand expiration, or peak inspiration, will be determined to be the phaseor phases of interest, and in such embodiments step 640 would only checkwhether sufficient number of pulses (e.g., 1, 5, or 10) were delivered630 coinciding with the phase or phases of interest.

In some embodiments, step 640 will only be satisfied when apredetermined number of pulses have been delivered in each respiratoryphase of interest. For example, a device could be programmed to checkfor phrenic nerve activation 650 only after 10 pulses have beendelivered in each respiratory phase of interest (e.g., check whether anyof the previously delivered 10 pulses activated the phrenic nerve). Suchembodiments allow for repeatedly testing specific pacing parametersduring one or more respiratory phases of interest, which in somecircumstances may produce more reliable results then testing pacingparameters a fewer number of times.

As discussed above, step 640 represents a check to determine whether asufficient number of pulses having been delivered in satisfaction ofpredetermined criteria, where if not enough pulses have been delivered620 then the method 600 continues or resumes delivering 620 cardiacpacing pulses according to the cardiac pacing schedule while holdingpacing energy parameters constant until the criteria are satisfied. Inthis way, the method 600 essentially dwells at the current pacingparameter over one or more respiratory cycles and delivers 620 pacingpulses during various cycle phases to determine the influence ofrespiratory phase on phrenic nerve activation until pacing pulseparameter settings are found that reliably do not activate the phrenicnerve.

If phrenic nerve activation is detected 650 for any of the delivered 620pulses, then the method 600 decrements 660 the current pacing pulseparameter setting. For example, if the current pacing pulse parametersetting was 1.6 volts at delivery 620, and phrenic nerve activation wasdetected 650 (e.g., phrenic nerve activation associated with one or morepulses delivered 620 during peak inspiration), then the pulse voltagesetting can be decremented to 1.5 volts. Other parameters (e.g., pulseduration) can be scanned and decremented (or incremented in scan-upembodiments) in different amounts.

Steps 620-630-640-650-660 can be executed in a loop, decrementing 660the pacing parameter with each turn of the loop, until phrenic nerveactivation is lost for all respiration cycle phases of interest. Whenphrenic nerve activation is detected 650 to be lost for all respirationcycle phases of interest, the parameter levels to which the cardiacpacing parameters were decremented 660 to can be set 670 as cardiacpacing parameters for subsequent therapy (or a further decremented valuecan be used to provide a safety margin). The set 670 cardiac pacingparameters can then be used for therapy delivery, which provides someassurance that phrenic nerve stimulation is unlikely. The method 600 canthen be initiated once again as discussed above, such as by thedetection of phrenic nerve stimulation months or years after the cardiacpacing parameters have been set 670 and used for therapy.

In the method 600 of FIG. 6, the pacing pulses are delivered 620according to a cardiac pacing schedule, such that a regimen of cardiacpaces consistent with a prescribed cardiac therapy is maintainedthroughout testing for phrenic nerve activation. In this way, thecoinciding of pulses and respiratory phases of interest occurs randomly,as alignment depends on the cardiac pacing schedule (which itself couldbe based on one or more physiologic parameters such as intrinsic atrialactivity and/or patient activity level) and natural patient breathing.In this way, the timing of cardiac pacing pulse delivery is not based onthe respiration cycle of the patient. In some other embodiments, thepulses can be delivered 620 in a manner specifically timed for themonitored 610 phases of interest, such as by changing anartioventricular delay. However, the method 600 as illustrated dwells insteps 620-640 through enough respiratory cycles until pulses aredelivered during all phases of interest, wherein no pulse timingadjustment is made based on respiration (i.e. the pulse timing isdependent on cardiac parameters, such as the normal course of cardiacresynchronization therapy, and not respiratory parameters).

FIG. 7 illustrates a method 700 for characterizing a patient's phrenicnerve activation transition zone. The method 700 includes initiating 710a phrenic nerve activation test. Initiation 710 can occur in the samemanner as in the method 600 of FIG. 6 (e.g., sensing phrenic nervestimulation).

Part of initiating 710 can include setting a current parameter level.The method 700 of FIG. 7 is generally directed to a step-down test,although the method 700 could be adapted to a step-up test. The method700 further includes delivering 720 at least one pacing pulse to theheart using the current pacing parameter settings, which can be thelevels set in the initiation 710. During and/or after delivery 720,accelerometer signals can be obtained and evaluated 730. Although step720 pertains to the use of accelerometer signals, any type of signalthat indicates phrenic nerve activation can additionally oralternatively be used. The accelerometer signal can be evaluated in anymanner discussed herein to detect phrenic nerve activation 735 (e.g., inthe manner of FIGS. 3-4).

If phrenic nerve activation is not detected 735, the method 700 advancesto step 750. If phrenic nerve stimulation is detected, the method 700advances to step 740 where the current pacing parameter level isdecremented (e.g., reduced in voltage and/or pulse duration). In thisway, the method 700 can loop through steps 720-730-735-740 until phrenicnerve activation is not detected 735 and an upper transition zoneboundary is identified 750 (e.g., the upper transition zone boundary isidentified as the parameter level at which phrenic nerve activation isfirst lost in a step-down scan).

In the embodiment of FIG. 7, respiration phase becomes particularlyimportant once the decrementing scan reaches the upper transitionboundary, as within the transition zone phrenic nerve activation becomesdependent on the respiratory cycle phase. As such, respiration signalsare obtained 760 to identify respiration phases, such as using thetechniques discussed herein. Such signals may include impedance, amongother signals. Respiration signals can be obtained 760 at any timeduring the method 700, including during step 770.

In step 770, a least one cardiac pacing pulse is delivered in each typeof respiration phase of interest using the current pacing parametersetting. For example, the phases of interest may be inspiration, peakinspiration, and expiration. Occurrence of these phases is identifiedbased on the obtained 760 respiration signals. The goal is not todeliver a pacing pulse during each occurrence of these phases for eachrespiratory cycle, but rather to complete step 770 by at some pointdelivering one pacing pulse during one occurrence of each phase ofinterest, even if over many respiratory cycles. For example, if thephases of interest are inspiration, peak inspiration, and expiration,then step 770 could be complete when a first pulse is delivered duringone instance of inspiration, a second pulse is delivered during oneinstance of peak inspiration, and a third pulse is delivered during oneinstance of expiration. It may take many respiration cycles while adevice dwells at the current pulse parameter settings before theopportunity arises for a device to deliver the necessary pulses tocomplete step 770.

There are various ways to deliver a least one pacing pulse in each typeof respiration phase of interest using the current pacing parametersetting. For example, the timing of the pace pulses of step 770 could bebased on a cardiac therapy schedule, where the pacing parameters energylevels are held constant during normal pacing operation until cardiacpulses just happen to be delivered in each type of respiration phase ofinterest. Again, it may take many respiration cycles before therespiration phases of interest and cardiac therapy schedule naturallyalign. Waiting for alignment in this way can be safer for a patient, asthis method prioritizes proper and consistent cardiac therapy overdeviating from a cardiac therapy schedule to expedite completion of thescan.

In some other embodiments, pacing pulse timing parameters, such asatrioventricular (AV) and left ventricular-right ventricular (VV) timingparameters, can be adjusted to cause alignment of a pacing pulse and arespiration phase of interest to complete step 770 (e.g., adjusting acardiac therapy schedule to force alignment of a pulse and a respiratorycycle phase of interest). In some cases, a device may wait for naturalalignment (e.g., according to a cardiac therapy schedule based oncardiac parameters and not based on respiration), but if a timer expireswithout completion of step 770, then the AV delay or some other timingparameter may be slightly adjusted to force alignment.

During step 770, accelerometer or other data indicative of phrenic nerveactivation can be taken and evaluated as in the manner of step 730.Using this data, it can be determined whether phrenic nerve activationwas detected 775 during any of the respiratory phases of interestcorresponding to a delivered 770 pacing pulse. If phrenic nerveactivation was detected 775 for any of the phases of interest in which apacing pulse was delivered 770, then the current pacing parameter isdecremented 780 and step 770 is repeated. In this way, steps 770-775-780can be repeated in a loop until a lower transition zone boundary isidentified 790. Identification 790 of the lower transition zone boundaryis based on the current pacing parameter settings when no phrenic nerveactivation was detected 775 from pacing pulses from 770.

In some embodiments, a set of cardiac pacing pulses (i.e. apredetermined number of pulses having common energy parameters) must bedelivered 770 during each type of respiratory phase of interest withoutany pulses of the set activating the phrenic nerve. Successive sets ofpulses decreasing in energy can be delivered until all of the pulses ofone of the sets do not cause phrenic nerve activation (e.g., 10 pulsesmust be delivered 770 during 10 occurrences of each type of phase ofinterest to satisfy step 770). For the energy parameters of the set thatdid not activate the phrenic nerve, it can be determined that theparameters are below the lower transition zone boundary 790. Sets ofcardiac pacing pulses can also be used in the same manner in the othermethods discussed herein (e.g., the methods of FIGS. 2 and 6).

In the method 700 of FIG. 7, a scan is conducted of one or more cardiacpacing pulse parameters in steps 720-730-735-740 without regard torespiration phase because phrenic nerve activation is not supposed to berespiration phase dependent above the transition zone. Once the uppertransition zone boundary is identified 750, the subsequent scanningtakes into account respiratory phase until the lower zone boundary isidentified 790, because phrenic nerve activation is respiratory phasedependent within the transition zone. Although not illustrated,subsequent scanning below the lower transition zone boundary (e.g.,step-down scan to identify the cardiac capture threshold) may not takeinto account respiratory phase, because phrenic nerve activation shouldnot be dependent on respiratory phase below the lower transition zoneboundary.

Some patients may not have a transition zone. In such cases, a devicecould carryout the methods discussed herein by equating the upperboundary with the lower boundary and this value would be deemed thephrenic nerve activation threshold. Some embodiments may not seek todefine both an upper and lower limit of a transition zone. For example,in a scan-down embodiment, only the lower zone boundary may be ofinterest, such that cardiac therapy pacing parameters can be set belowthe lower zone boundary once the lower zone boundary is found. Someembodiments may not seek to identify transition zone boundaries, butinstead just check whether phrenic nerve activation is dependent onrespiration phase for a pacing parameter level of interest by testingall respiration phases of interest at the pacing parameter level ofinterest (e.g., as if only steps 770-775-780 were performed).

The methods and devices disclosed herein can characterize a transitionzone within a strength-duration relationship. Cardiac capture isproduced by pacing pulses having sufficient energy to produce apropagating wavefront of electrical depolarization that results in acontraction of the heart tissue. Generally speaking, the energy of thepacing pulse is a product of two energy parameters—the amplitude of thepacing pulse and the duration of the pulse. Thus, the capture thresholdvoltage over a range of pulse widths may be expressed in a capturestrength-duration plot 810 as illustrated in FIG. 8.

Phrenic nerve activation by a pacing pulse is also dependent on thepulse energy. The phrenic nerve activation strength-duration plot 820for reliable undesirable activation may have a different characteristicfrom the capture strength-duration plot 810 and may have a relationshipbetween pacing pulse voltage and pacing pulse width.

FIG. 8 provides graphs illustrating a capture strength-duration plot 810associated with cardiac capture and a phrenic nerve activationstrength-duration plot 820 associated with reliable undesirablediaphragmic activation (e.g., phrenic nerve activation regardless ofrespiratory phase). A pacing pulse having a pulse width of W₁ requires apulse amplitude of V_(c1) to produce capture. A pacing pulse havingpulse width W₁ and pulse amplitude V_(c1) exceeds the voltage threshold,V_(u1), for an undesirable diaphragmic activation through phrenic nervestimulation. If the pulse width is increased to W₂, the voltage requiredfor capture, V_(c2), is less than the voltage required for undesirablediaphragmic activation, V_(u2). Therefore, pacing pulses can bedelivered at the pacing energy associated with W₂, V_(c2) to providecapture of the heart without causing the phrenic nerve activation.

The area to the right of the intersection 851 of the capture and phrenicnerve activation strength-duration plots 810, 820, between the phrenicnerve activation strength-duration 820 and capture strength-duration 810plots, defines a set of energy parameter values that produce capturewhile avoiding phrenic nerve activation. Pacing pulses within thisregion produce a more ideal therapy response (capture withoutundesirable stimulation).

The capture and phrenic nerve activation strength-duration plots 810,820 of FIG. 8 may be generated by delivering a number of test pulses atvarious amplitudes and pulse widths and evaluating whether cardiaccapture and undesirable stimulation occurred (e.g., using the methods ofFIGS. 1, 6, and/or 7). The capture and phrenic nerve activationstrength-duration plots 810, 820 can then be completed by interpolationand extrapolation based on, for example, an exponential fit. Suchmethods can minimize the number of test pulses required to fullycharacterize the relationships between pulse parameters and stimulation,thereby minimizing battery consumption and uncomfortable testing.Extrapolation and interpolation can also allow the relationships betweenpulse parameters and stimulation for a particular device configurationto be characterized beyond what the device itself is programmed to, orcapable of, performing. Methods and systems for determining and usingstrength-duration relationships are described in U.S. Pat. No.8,209,013, which is incorporated herein by reference in its entirety.

FIG. 8 also illustrates a transition zone 890 outlined by dashed linesand the phrenic nerve activation strength-duration plot 820. Thetransition zone 890 is the parameter range inside of which phrenic nerveactivation is dependent on the phase of the patient's respiration cycle.The transition zone 890 could be determined by scanning techniques, suchas by the method of FIG. 7 performed for both pulse voltage and durationparameters.

In programming a therapy device, it is generally desirable to program apacing device so as to not risk causing undesirable stimulation, such asphrenic nerve activation. Therefore, it can be desirable to selectpacing parameters that are not within a transition zone. Moreover, itcan be desirable to select pacing parameter settings below a transitionzone because the lower the pulse voltage and pulse duration the lessbattery energy is used for therapy. These aspects of therapy programmingcan make use of a strength-duration curve and transition zone, such asthat of FIG. 8.

For example, a doctor or system analyzing FIG. 8 may select a pacingpulse parameter (e.g., voltage) above the capture strength-duration plot810 but below the transition zone 890 as a setting that will reliablycapture the appropriate chamber (e.g., left ventricle) withoutoccasionally activating the phrenic nerve.

A doctor or system may select a voltage parameter based on the voltagerange above the capture strength-duration plot 810 and below thetransition zone 890. For example, some pacing protocols will vary thepulse voltage between pulses for various reasons during the normalcourse of therapy. A greater parameter range between capturestrength-duration plot 810 and the transition zone 890 indicates agreater parameter range within which a protocol (e.g., automaticventricular capture test) has to operate to vary a parameter (e.g.,pulse voltage). In the case of FIG. 8, a doctor or system may be morelikely to select a shorter pulse width because the shorter pulse widthsare associated with a greater range between the capturestrength-duration plot 810 and the transition zone 890 relative tolonger pulse widths. In this way, a doctor or system can select a pacingpulse parameter level (e.g., voltage or duration) based on thatparameter level having a greater range between a transition zone and athreshold (e.g., cardiac capture or phrenic nerve activation threshold)relative to other parameter levels.

If a doctor or system wanted or needed to use a parameter setting withina transition zone (e.g., if preferred therapy parameters were onlypossible within a transition zone) then the methods described hereincould inform the doctor that the device would need to be programmed totime pacing pulses (e.g., left ventricular pulses) with the respirationcycle to minimize phrenic nerve activation by avoiding delivering pulseswhen the respiration cycle is in the phase most susceptible to phrenicnerve activation identified for that particular patient and pace pulsesettings (e.g., vector and energy parameters) using the methods andsystems discussed herein. In some embodiments, a system couldautomatically avoid delivering pulses during respiratory phase or phasesthat are identified by the methods and systems discussed herein as mostsusceptible to phrenic nerve activation for a particular patient.

Multiple strength-duration plots having transition zones like the oneillustrated in FIG. 8 can be generated for multiple different electrodecombinations. Based on the strength-duration plots, a preferredelectrode combination can be selected for delivering therapy. Forexample, if one electrode combination is associated with a smallertransition zone then it may be preferable to select for therapy deliveryversus an electrode combination having a larger transition zone. In manycases, the electrode combination with the smaller transition zone wouldlikely correspond to the configuration having the greatest amount offlexibility in an operation that achieves a desired therapy outcome(e.g., capture without phrenic nerve activation). Parameter andelectrode selection in the ways described herein may be performed by ahuman or automatically by a processor executing stored programinstructions. Methods and systems for electrode combination selectionare described in United States Patent Application Publication No.2009/0043351, which is incorporated herein by reference in its entirety.

In some embodiments, a preferred electrode combination for deliveringpacing therapy can be selected (e.g., by a human or controller) on thebasis of which combination has the greatest range between the capturestrength-duration plot 810 and the detected pacing settings at whichphrenic nerve activation is not detected for any respiratory phases(e.g., as determined by the methods of FIGS. 1, 6, and/or 7). Selectingon the basis of such a range gives an automated therapy program the mostrange in which to modify a parameter (e.g., voltage) as needed overtime.

Various embodiments not only test various energy parameters tocharacterize a patient's phrenic nerve activation response, but alsotest various electrode combinations used for pace pulse delivery. Forexample, an embodiment according to FIG. 6 could additionally oralternatively switch electrode combinations for step 660, cyclingthrough various electrode combinations by repeating steps620-620-640-650-660 until a vector is found that is not associated withphrenic nerve activation for any phases of respiration. An electrodecombination can then be selected and used for cardiac therapy deliverybased on which electrode combination has preferable energy parameters(e.g., lowest capture threshold) that is not associated with phrenicnerve activation for any phases of respiration at those preferableenergy parameters. The other embodiments discussed herein (e.g., FIGS.1-10) can likewise test different electrode combinations and facilitatevector selection based on which vector or vectors provide a beneficialtherapeutic response using preferable energy parameters that are notassociated with phrenic nerve activation for any phases of respirationat those preferable energy parameters.

In some embodiments, the particular phase or phases of a patient'srespiration cycles in which phrenic nerve stimulation occurs can beidentified. For example, only during certain phases of the respiratorycycle are some patients particularly susceptible to phrenic nervestimulation at certain pacing parameter settings. As such, variousembodiments can determine which respiratory phase(s) are associated withphrenic nerve activation and which are not, such as by using the methodsdescribed herein in connection with FIGS. 1-10. Therefore, pacing pulsescan only be delivered during those phases which are not associated withphrenic nerve stimulation and/or pacing therapy timing parameters can beadjusted (e.g., artioventricular delay and/or biventricular delay) canbe automatically adjusted as needed to avoid delivering a pacing pulseduring a respiratory phase determined to be associated with phrenicnerve stimulation.

The methods and techniques described herein can be used to identifydifferent thresholds for different respiration phases. For example, thescanning aspects of FIGS. 1, 6, and/or 7 can be used to identify aphrenic nerve activation threshold for each phase of interest, such asinspiration, peak inspiration, expiration, and non-breathing, bydelivering cardiac pacing pulse during these phases and scanning acrossone or more pulse energy parameters. For example, FIG. 1 can be used todetermine at which voltage a patient's phrenic nerve will be activatedby a cardiac pacing pulse delivered during inspiration. The same can bedone for the other respiratory phases, such that 4 different phrenicnerve activation thresholds will be identified, one for each phase ofrespiration. This information can then be used for therapy delivery. Forexample, the 4 phrenic nerve activation thresholds can be automaticallyprogrammed for use during CRM therapy delivery. During therapy deliverya device can monitor respiratory phase, and depending on whichrespiratory phase a patient is in when it is desired to deliver acardiac pacing pulse, pulse energy level can be varied in accordancewith the phrenic nerve activation threshold of the current respiratoryphase. Considering that heart rate is typically faster than respiratoryrate, several cardiac pacing pulses could be delivered during a singlerespiratory cycle, the energy level of each pulse adjusted to be belowthe phrenic nerve activation threshold of the current respiratory phase.

A cardiac rhythm management system configured to carry out such methodscan comprise an implantable cardiac pacing device having a plurality ofelectrodes configured for implantation in a patient; circuitryconfigured to output a plurality of cardiac pacing pulses through theelectrodes and modify one or more pacing parameters of the plurality ofcardiac pacing pulses; a phrenic nerve activation sensor configured tooutput a phrenic nerve activation signal indicative of activation of thepatient's phrenic nerve; a respiration sensor configured to output arespiration signal indicative of inhalation and exhalation respiratoryactivity of the patient; and a controller configured to execute programinstructions stored in memory to cause the system to identify aplurality of different respiratory phases based on the respirationsignal for multiple respiratory cycles of the patient, deliver theplurality of cardiac pacing pulses within each of the identifiedplurality of different respiratory phases, analyze the phrenic nervestimulation signal to identify respective phrenic nerve activationthresholds for a plurality of different respiratory phases based on thephrenic nerve activation signal, identify cardiac pacing pulseparameters for each of the plurality of respiratory phases based on therespective phrenic nerve activation thresholds for the plurality ofrespiratory phases, and deliver a cardiac pacing pulse therapy byvarying pulse energy output based on which respiratory phase each pacingpulse of the therapy is to be delivered in using the identified cardiacpacing pulse parameters.

FIG. 9 is a block diagram of a CRM device 900 that may incorporatecircuitry employing phrenic nerve activation detection algorithms inaccordance with embodiments of the present invention. The CRM device 900includes pacing therapy circuitry 930 that delivers pacing pulses to aheart. The CRM device 900 may optionally includedefibrillation/cardioversion circuitry 935 configured to deliver highenergy defibrillation or cardioversion stimulation to the heart forterminating dangerous tachyarrhythmias.

The pacing pulses are delivered via multiple cardiac electrodes 905(using electrode combinations), which can be disposed at multiplelocations within a heart, among other locations. Two or more electrodesmay be disposed within a single heart chamber, such as the leftventricle. The electrodes 905 are coupled to switch matrix 925 circuitryused to selectively couple electrodes 905 of various pacingconfigurations to signal processor 901, pacing therapy circuitry 930,defibrillation/cardioversion circuitry 935, and/or other components ofthe CRM device 900.

The CRM 900 device also includes a phrenic nerve activation sensor 910.The phrenic nerve activation sensor 910 can output a signal and/or otherinformation to signal processor 901 and control processor 940. Phrenicnerve activation sensor 910 may include an accelerometer, electricalsignal sensors (e.g., EMG, impedance), pressure sensor, acousticsensors, and/or any other sensor that can detect phrenic nerveactivation. Phrenic nerve activation sensor 910 may be implemented usinga discrete sensor or via software executed by a processor (e.g., controlprocessor 940) of the CRM device.

The control processor 940 can use information received from the signalprocessor 901, the phrenic nerve activation sensor 910, memory 945, andother components to implement phrenic nerve activation characterizationand avoidance algorithms, as disclosed herein.

For example, the pacing therapy circuitry 930 can provide informationregarding when a pacing pulse was delivered and the parameters of thepacing pulse, the phrenic nerve activation sensor 910 can provideinformation regarding sensed phrenic nerve activation, and signalprocessor 901 can provide information regarding transthoracic impedance(measured between electrodes 905). This information can be used toidentify respiratory cycle phases, phrenic nerve activation, phrenicnerve activation transition zones, and manage therapy delivery to avoidphrenic nerve activation, among other things.

Amplitude, peak timing, and/or correlation of delivered pulses tophrenic nerve activation (beat-to-beat and/or over time) can be usedwith a phrenic nerve activation signal in either the time or frequencydomain to determine whether one or more pacing pulses caused phrenicnerve stimulation.

A CRM device 900 typically includes a battery power supply (not shown)and communications circuitry 950 for communicating with an externaldevice programmer 960 or other patient-external device. Information,such as data, parameter information, evaluations, comparisons, data,and/or program instructions, and the like, can be transferred betweenthe device programmer 960 and patient management server 970, CRM device900 and the device programmer 960, and/or between the CRM device 900 andthe patient management server 970 and/or other external system. In someembodiments, the processor 940, memory 945, and/or signal processor 901may be components of the device programmer 960, patient managementserver 970, and/or other patient external system.

The CRM device 900 also includes memory 945 for storing executableprogram instructions and/or data, accessed by and through the controlprocessor 940. In various configurations, the memory 945 may be used tostore information related to thresholds, parameters, measured values,transitions zones, phrenic nerve activation patterns, programinstructions, and the like.

The circuitry represented in FIG. 9 can be used to perform the variousmethodologies and techniques discussed herein. Memory 945 can be acomputer readable medium encoded with a computer program, software,firmware, computer executable instructions, instructions capable ofbeing executed by a computer, etc. to be executed by circuitry, such ascontrol processor 940. For example, memory 945 can be a computerreadable medium storing a computer program, execution of the computerprogram by control processor 940 causing delivery of pacing pulsesdirected by the pacing therapy circuitry, reception of one or moresignals from phrenic nerve activation sensors 910 and/or signalprocessor 901 to identify phrenic nerve activation transition zones andmanage therapy parameters to avoid phrenic nerve activation inaccordance with the various methods and techniques made known orreferenced by the present disclosure. In similar ways, the other methodsand techniques discussed herein can be performed using the circuitryrepresented in FIG. 9.

The methods and devices discussed herein can collect electrical signals,such as impedance signals indicative of respiration and electricalcardiac signals indicative of heart activity, using electrodes. Suchelectrodes can include implanted electrodes 905 and/or externalelectrodes, such as skin electrodes (not shown).

The therapy device 1000 illustrated in FIG. 10 employs circuitry capableof implementing phrenic nerve activation detection algorithm techniquesdescribed herein. The therapy device 1000 includes CRM circuitryenclosed within an implantable housing 1001. The CRM circuitry iselectrically coupled to an intracardiac lead system 1010. Although anintracardiac lead system 1010 is illustrated in FIG. 10, various othertypes of lead/electrode systems may additionally or alternatively bedeployed. For example, the lead/electrode system may comprise anepicardial lead/electrode system including electrodes outside the heartand/or cardiac vasculature, such as a heart sock, an epicardial patch,and/or a subcutaneous system having electrodes implanted below the skinsurface but outside the ribcage.

Portions of the intracardiac lead system 1010 are shown inserted intothe patient's heart. The lead system 1010 includes cardiac pace/senseelectrodes 1051-1056 positioned in, on, or about one or more heartchambers for sensing electrical signals from the patient's heart and/ordelivering pacing pulses to the heart. The intracardiac sense/paceelectrodes, such as those illustrated in FIG. 10, may be used to senseand/or pace one or more chambers of the heart, including the leftventricle, the right ventricle, the left atrium and/or the right atrium.The CRM circuitry controls the delivery of electrical stimulation pulsesdelivered via the electrodes 1051-1056. The electrical stimulationpulses may be used to ensure that the heart beats at a hemodynamicallysufficient rate, may be used to improve the synchrony of the heartbeats, may be used to increase the strength of the heart beats, and/ormay be used for other therapeutic purposes to support cardiac functionconsistent with a prescribed therapy while avoiding phrenic nerveactivation.

The lead system 1010 may include defibrillation electrodes 1041, 1042for delivering defibrillation/cardioversion pulses to the heart.

The left ventricular lead 1005 incorporates multiple electrodes 1054a-1054 d and 1055 positioned at various locations within the coronaryvenous system proximate the left ventricle. Stimulating the ventricle atmultiple locations in the left ventricle or at a single selectedlocation may provide for increased cardiac output in patients sufferingfrom heart failure (HF), for example, and/or may provide for otherbenefits. Electrical stimulation pulses may be delivered via theselected electrodes according to a timing sequence and outputconfiguration that enhances cardiac function. Although FIG. 10illustrates multiple left ventricle electrodes, in other configurations,multiple electrodes may alternatively or additionally be provided in oneor more of the right atrium, left atrium, and right ventricle.

Portions of the housing 1001 of the implantable device 1000 mayoptionally serve as one or more multiple can 1081 or indifferent 1082electrodes. The housing 1001 is illustrated as incorporating a header1089 that may be configured to facilitate removable attachment betweenone or more leads and the housing 1001. The housing 1001 of the therapydevice 1000 may include one or more can electrodes 1081. The header 1089of the therapy device 1000 may include one or more indifferentelectrodes 1082. The can 1081 and/or indifferent 1082 electrodes may beused to deliver pacing and/or defibrillation stimulation to the heartand/or for sensing electrical cardiac signals of the heart. One or moreaccelerometers can be provided on and/or within the housing 1001, header1001, or lead system 1010 for sensing phrenic nerve activation.

Communications circuitry is disposed within the housing 1001 forfacilitating communication between the CRM circuitry and apatient-external device, such as an external programmer or advancedpatient management (APM) system. The therapy device 1000 may alsoinclude sensors and appropriate circuitry for sensing a patient'smetabolic need and adjusting the pacing pulses delivered to the heart toaccommodate the patient's metabolic need.

Impedance can be measured to track respiration phases. In someembodiments, measurement of impedance involves an electrical stimulationsource, such as an exciter. The exciter delivers an electricalexcitation signal, such as a strobed sequence of current pulses or othermeasurement stimuli, to the heart between the electrodes. In response tothe excitation signal provided by an exciter, a response signal, e.g.,voltage response value, is sensed by impedance detector circuitry, suchas that in a signal processor. From the measured voltage response valueand the known current value, the impedance of the electrode combinationmay be calculated.

For example, a small current can be injected through electrodes 905 (ofFIG. 9) by pacing therapy circuitry 930 or other components. Theimpedance between two or more electrodes 905 is then measured, changesin which can reflect the phases of respiration as shown in FIG. 2. Theelectrodes could be skin surface electrodes or subcutaneous electrodes.Different electrode pairs could be used. For example, any pair orgrouping of electrodes of FIG. 10 can be used to measure impedance,including lead-to-lead (e.g., 1055-1041), lead-to-can (e.g., 1053-1081),and can-to-can (e.g., 1081-1082) measurements.

Techniques and circuitry for determining the impedance of an electrodecombination is described in commonly owned U.S. Pat. No. 6,076,015 whichis incorporated herein by reference in its entirety.

In some implementations, an APM system may be used to perform some ofthe processes discussed herein, including evaluating, estimating,comparing, detecting, selecting, and updating, among others. Methods,structures, and/or techniques described herein, may incorporate variousAPM related methodologies, including features described in one or moreof the following references: U.S. Pat. Nos. 6,221,011; 6,270,457;6,277,072; 6,280,380; 6,312,378; 6,336,903; 6,358,203; 6,368,284;6,398,728; and 6,440,066, which are hereby incorporated herein byreference in each of their respective entireties.

In certain embodiments, the therapy device 1000 may include circuitryfor detecting and treating cardiac tachyarrhythmia via defibrillationtherapy and/or anti-tachyarrhythmia pacing (ATP). Configurationsproviding defibrillation capability may make use of defibrillation coils1041, 1042 for delivering high energy pulses to the heart to terminateor mitigate tachyarrhythmia.

CRM devices using multiple electrodes, such as illustrated herein, arecapable of delivering pacing pulses to multiple sites of the atriaand/or ventricles during a cardiac cycle. Certain patients may benefitfrom activation of parts of a heart chamber, such as a ventricle, atdifferent times in order to distribute the pumping load and/ordepolarization sequence to different areas of the ventricle. Amulti-electrode pacemaker has the capability of switching the output ofpacing pulses between selected electrode combinations within a heartchamber during different cardiac cycles.

Commonly owned U.S. Pat. No. 6,772,008, which is incorporated herein byreference, describes methods and systems that may be used in relation todetecting undesirable tissue stimulation. Muscle stimulation may bedetected, for example, through the use of an accelerometer and/or othercircuitry that senses accelerations indicating muscle movements (e.g.,diaphragmatic) that coincide with the output of the stimulation pulse.Other methods of measuring tissue stimulation (e.g., phrenic nerveactivation) may involve, for example, the use of an electromyogramsensor (EMG), microphone, and/or other sensors. For example, phrenicnerve activation may be automatically detected using a microphone todetect the patient's expiration response to undesirable diaphragmicactivation due to electrical phrenic nerve activation.

Undesirable nerve or muscle stimulation may be detected by sensing aparameter that is directly or indirectly responsive to the stimulation.Undesirable nerve stimulation, such as stimulation of the vagus orphrenic nerves, for example, may be directly sensed usingelectroneurogram (ENG) electrodes and circuitry to measure and/or recordnerve spikes and/or action potentials in a nerve. An ENG sensor maycomprise a neural cuff and/or other type or neural electrodes located onor near the nerve of interest. For example, systems and methods fordirect measurement of nerve activation signals are discussed in U.S.Pat. Nos. 4,573,481 and 5,658,318 which are incorporated herein byreference in their respective entireties. The ENG may comprise a helicalneural electrode that wraps around the nerve (e.g., phrenic nerve) andis electrically connected to circuitry configured to measure the nerveactivity. The neural electrodes and circuitry operate to detect anelectrical activation (action potential) of the nerve followingapplication of the cardiac pacing pulse.

Neural activation can be detected by sensing a surrogate parameter thatis indirectly responsive to nerve stimulation. Lung pressure, pleuralpressure, thoracic pressure, airway pressure, and thoracic impedance areexamples of parameters that change responsive to stimulation of thephrenic nerve. In some embodiments, a patient's airway pressure may bemeasured during and/or closely following delivery of electricalstimulation. The detected change in pressure may be related tostimulation of the phrenic nerve.

Undesirable stimulation threshold measuring may be performed byiteratively increasing, decreasing, or in some way changing a voltage,current, duration, energy level, and/or other therapy parameter betweena series of test pulses. One or more sensors can monitor for undesirableactivation immediately after each test pulse is delivered. Using thesemethods, the point at which a parameter change causes undesirablestimulation can be identified as a stimulation threshold.

By way of example and not by way of limitation, the undesirablestimulation threshold for a particular electrode combination may bemeasured by delivering a first test pulse using the initial electrodecombination. During and/or after each test pulse is delivered, sensorscan monitor for undesirable stimulation. For example, an accelerometermay monitor for movement of the diaphragm indicating that the test pulsestimulated the phrenic nerve and/or diaphragm muscle. If no phrenicnerve and/or diaphragm muscle stimulation is detected after delivery ofa test pulse, then the test pulse is increased a predetermined amountand another test pulse is delivered. This scanning process ofdelivering, monitoring, and incrementing is repeated until phrenic nerveand/or diaphragm muscle stimulation is detected. One or more of the testpulse parameters at which the first undesirable stimulation is detectedcan be considered to be the undesirable stimulation threshold.

The various steps of FIGS. 1, 6, and 7, as well as the other steps andmethods disclosed herein, can be performed automatically, such that nodirect human assistance (e.g., physician and/or patient) is needed toinitiate or perform the various discrete steps. Alternatively, thevarious steps of this disclosure can be performed semi-automaticallyrequiring some amount of human interaction to initiate or conduct one ormore steps.

The various steps of FIGS. 1, 6, and 7, as well as other methods andsteps discussed herein, can be initiated upon implant, by a physician,upon detection of a change in condition, and/or periodically. Conditionchanges that could initiate the processes include detection of phrenicnerve activation, loss of capture, change in posture, change in diseasestate, detection of non-therapeutic activation, and/or short or longterm change in patient activity state, for example.

Periodic and/or condition initiated testing to update capture threshold,phrenic nerve activation threshold, and device relationship informationcan be useful to monitor for certain conditions that might not otherwisebe readily apparent but warrant attention and/or a therapy change.Device and/or physiologic changes may alter the effect of pacing pulses.For example, device component defects, lead migration, electrodeencapsulation, and/or physiologic changes may increase the pacing pulseamplitude needed to reliably produce capture and/or decrease the pacingpulse amplitude needed to stimulate the phrenic nerve, leading touncomfortable and ineffective pacing therapy. Updated capture threshold,phrenic nerve activation threshold, transition zones, and devicerelationship information can be used to automatically reprogram thetherapy device and/or alert a physician to reconfigure the therapydevice.

The various processes illustrated and/or described herein (e.g., theprocesses of FIGS. 1, 6, and 7) can be performed using a single deviceembodiment configured to perform each of the processes (e.g., thecircuitry of FIG. 9 in the configuration of FIG. 10) that concern theconcepts illustrated and discussed in connection with FIGS. 2-5 and 8.

Sensors that can be used for detection of phrenic nerve activation arealso used for rate-adaptive pacing. Rate-adaptive pacemakers aretypically used to treat patients who are chronotropically incompetent.In these devices, patient activity and/or metabolic demand aredetermined and the patient activity/metabolic demand information can beused to control the pacing rate. A number of sensor types have been usedfor rate control. Motion sensors, such as accelerometers, piezoelectricsensors, and/or magnetic ball sensors, are widely used for detecting thevibration caused by patient activity. Accelerometers sense motion of thepatient's body and are used in systems that have the capability toprovide rapid rate responsiveness based on patent activity. However,accelerometer-based activity sensors can be fooled by motion that is notrelated to patient activity, such as riding in a car on a bumpy road,which may trigger inappropriate increases in pacing rate.

Although sometimes more complex than accelerometer-based activitysensors, minute ventilation (MV) sensors are also frequently used tocontrol pacing rate. MV sensors detect patient respiration and derivefrom the respiration signal the amount of air moved in one minute. MVsensors offer several advantages over accelerometers because MV sensorscan appropriately increase pacing rate during periods that heart ratewould naturally increase without a concurrent increase in patientactivity, such as during periods that the patient experiences intenseemotion. Other types of sensors have also been used or proposed forrate-adaptive pacing, e.g., sensors based on QT interval, peakendocardial acceleration, pre-ejection interval, etc. Pacing ratecontrol using multiple sensors may also be used, such as by blending thesensor outputs.

The output of a rate-adaptation sensor is used to generate a sensorindicated rate (SIR) which controls the pacing rate when the pacemakeris operating in a rate-responsive pacing mode. The output of therate-adaptation sensor is processed with characteristics of theprocessing, e.g., sampling rate, gain, offset, and filteringcharacteristics, selected to enhance the detection of changes inactivity and/or metabolic demand.

Some types of sensors used to control rate-adaptive pacing, e.g., MVsensors and accelerometers, also respond to skeletal muscle contractionscaused by phrenic nerve activation. Because sensors used to controlrate-adaptive pacing are already well known and are readily available ina large number of cardiac devices, it is desirable to use the samesensor for both rate-adaptive pacing control and detection of phrenicnerve stimulation. However, the signal processing requirements foroptimally sensing rate-adaptation parameters, such as activity ormetabolic demand, are different from the signal processing requirementsfor optimally detecting phrenic nerve activation.

Embodiments of the invention are directed to approaches employing asingle sensor that is used both for sensing rate-adaptation parameters,such as patient activity or metabolic demand and for detecting phrenicnerve activation. The sensor signal is processed using first signalprocessing characteristics that are selected for optimal sensing of arate-adaptation parameter, e.g., MV or activity. The sensor signal isprocessed using second signal processing characteristics that areselected for optimal phrenic nerve activation detection.

In some implementations, the sensor signal 1107 is processed using twoseparate signal processing channels as illustrated in FIG. 11A. Theoutput terminal 1106 of the sensor 1105 (e.g., MV sensor, activitysensor) used to control rate-adaptive pacing is coupled to a firstsignal processing channel 1110 and to a second signal processing channel1120. The first and second signal processing channels 1110, 1120 includefirst and second signal processing circuitry 1111, 1121, respectively.The first signal processing circuitry 1111 has a first set of signalprocessing characteristics that are selected for determining patientactivity or metabolic demand and which are used to process the sensorsignal 1107. The second signal processing circuitry 1121 has a secondset of signal processing characteristics that are selected for detectingphrenic nerve activation and which are used to process the sensor signal1107. The signal processing channels 1110, 1120 may include analogcomponents, digital components or a mixture of analog and digitalcomponents.

In one example, the first signal processing circuitry 1111 includes oneor more filters configured to attenuate certain frequencies of thesensor signal. The second signal processing circuitry 1121 may alsoinclude one or more filters configured to attenuate frequencies of thesensor signal. The filter characteristics of the first filters aredifferent from those of the second filters. In some implementations, thefirst signal processing circuitry 1111 includes amplifier circuitry thathas different amplifier characteristics from the amplifiercharacteristics of the second signal processing circuitry 1121. In someimplementations, one or both of the first signal processing circuitry1111 and the second signal processing circuitry may include an A/Dconverter for converting the analog sensor signal 1107 to a digitalsignal. The A/D conversion characteristics of the first signalprocessing circuitry (n-bit resolution, sampling rate, etc.) may bedifferent from the A/D conversion characteristics of the second signalprocessing circuitry. In some implementations, only one of the signalprocessing channels 1110, 1120 includes an A/D converter, so that thesignal processing performed by one of the channels 1110, 1120 isachieved predominantly by analog signal processing and the signalprocessing performed by the other of the channels 1120, 1110 is achievedby digital signal processing.

In some configurations, pre-processing circuitry 1109, e.g., amplifiers,analog and/or digital filter components, and/or an A/D converter may beinterposed in the signal path 1107 between the sensor output terminal1106 and the signal processing channels 1110, 1120. The pre-processingcircuitry may provide A/D conversion, pre-filtering or pre-amplificationfunctions applied to the output of the sensor to produce the signal1107.

Consider an implementation that uses an accelerometer (e.g., single axisor multi-axis accelerometer) to determine patient activity which in turnis used to develop a sensor indicated rate (SIR) for adapting the pacingrate. As the patient engages in activity, such as running or walking,the output of the accelerometer tracks the patient movement. Themodulation in the accelerometer signal caused by patient movementincludes relatively low frequency components, typically between about 1and 10 Hz. Therefore, frequencies less than about 1 Hz and greater thanabout 10 Hz are noise with respect to patient activity and it isdesirable to remove these signals from the activity signal, such as byusing a band pass filter.

On the other hand, activation of the phrenic nerve causes an abruptcontraction of the skeletal muscle of the diaphragm similar to a hiccupreflex. This abrupt contraction produces an accelerometer signal havingfrequency components which are greater than about 5 Hz, and arediscernibly higher than the frequency components associated with patientactivity signal. Thus, it is desirable to filter out lower frequenciespredominantly associated with patient motion to enhance detection of thehigher frequency components associated with phrenic nerve activation. Ifa signal processed for activity sensing is used for phrenic nerveactivation, low frequency deflections in a signal filtered for activitysensing, e.g., signal spikes on the order of about 4-6 Hz, can causeerroneous phrenic nerve activation detection. Optimally processing theaccelerometer signal for detection of phrenic nerve activation involvesat least filtering to attenuate frequencies less than about 5 Hz.

In some cases, additional filtering may further enhance the signal forphrenic nerve activation detection. For example, heart sounds canmodulate the accelerometer signal and may interfere with phrenic nerveactivation detection. In some embodiments, one or more notch filters maybe used to attenuate noise frequencies in the sensor signal. Forexample, a notch filter which is adaptive based on cardiac rate may beused to attenuate the band of frequencies associated with heart soundsin the accelerometer signal.

FIG. 12 illustrates the output of an activity sensor (accelerometer)before and after processing by two different signal processing circuits.Graph 1210 shows the unfiltered accelerometer signal. Graph 1220 showsthe accelerometer signal using filter characteristics suitable foractivity sensing. Graph 1230 shows the accelerometer signal processedusing filter characteristics selected for detection of phrenic nerveactivation. At times t₁ and t₃, phrenic nerve activations 1201, 1202occur. Graphs 1210 and 1220 show deflections 1211, 1221, 1212, 1222 thatare marginally detectable over background noise. At time t₂ the patientmoves, causing a deflection 1215 in graph 1210 and a deflection 1225 ingraph 1220 associated with the patient motion. The deflections 1215 and1225 in graphs 1210, 1220 caused by patient motion could result in anerroneous phrenic nerve activation detection if the signal 1220 filteredfor activity sensing was used.

Graph 1230 illustrates the accelerometer signal processed using filtercharacteristics selected for optimal detection of phrenic nerveactivation. As can be seen in FIG. 12, the phrenic nerve activations1201, 1202 that occur at times t₁ and t₃ cause deflections 1231 and 1232which have a much higher signal to noise ratio than deflections 1211,1212 in the unfiltered activity signal 1210 or deflections 1221, 1222 inthe activity signal. Additionally, the patient movement at time t₂ isattenuated and does not cause a deflection in graph 1230, thus avoidingthe potential for an erroneous detection of phrenic nerve activation.

Consider an implementation that uses an MV sensor to determine thepatient's metabolic demand for adapting the pacing rate. An MV sensorcan be implemented by measuring thoracic impedance which is modulated byrespiration. Thoracic impedance measurement circuitry includes drivecircuitry and impedance measuring circuitry. The drive circuitrysupplies a current signal of a specified amplitude, such as one or moreconstant current pulses, to drive electrodes that are disposed in thepatient's thorax. Voltage sense electrodes are disposed at locationswithin the thorax so that the difference in potential between thevoltage sense electrodes during the current pulses is representative ofthe thoracic impedance between the voltage sense electrodes. Cardiacelectrodes, including intracardiac electrodes and/or the conductivehousing or can of an implantable pacemaker or defibrillator, can be usedas drive electrodes and/or voltage sense electrodes. The impedancemeasuring circuitry processes the voltage sense signal from the voltagesense electrodes to derive the impedance signal. The impedance signal ismodulated by respiration and thus provides the respiration signal asillustrated in FIG. 2. Minute ventilation (MV) is derived from therespiration signal as the amount of air inhaled or exhaled in oneminute.

As the patient engages in physical activity, or otherwise experiences anincrease in metabolic demand, the depth and/or rate of respirationincreases which causes an increase in the measured MV. The value of theMV is used in rate-adaptive pacing to calculate the sensor indicatedrate (SIR). The respiration signal from which MV and the SIR arecalculated, includes relatively low frequency components. For example,normal breathing at about 12 breaths/minute causes oscillations in thethoracic impedance signal at about 0.2 Hz. In contrast, phrenic nerveactivation produces a reflex having frequency components similar to ahiccup reflex, with modulation of the thoracic impedance signal atfrequencies that are substantially higher than normal breathing. Forexample, the inspiratory duration of the phrenic nerve activation may beless than about 150 ms, whereas the inspiratory duration of normalbreathing is closer to about 1 to 2 sec.

FIG. 13 depicts three graphs 1310, 1320, 1330 representing the thoracicimpedance signal that is produced using different three sets of signalprocessing characteristics. The first graph 1310 illustrates arespiration signal processed by circuitry that is selected to detectrespiration cycles and determine MV. For example, to obtain signal 1310,the output of the thoracic impedance sensor may be digitized using asampling rate of about 20 Hz and filtered to remove noise including thecardiac component of the signal. In FIG. 1310, the thoracic impedancesensor is filtered using a bandpass filter. The low frequency cut offmay be about 0.1 Hz. The high pass cut off frequency of the bandpassfilter may be adaptable to substantially attenuate the cardiac componentand/or other noise from the sensor signal. The high frequency cut offmay be adaptable in a range, e.g., from about 0.5 Hz to up to about 4Hz. For example, an upper frequency cutoff of about 1.5 Hz may be usedto substantially attenuate the cardiac component for heart rates up toabout 90 bpm. An upper frequency cutoff of about 4 Hz may be used tosubstantially attenuate the cardiac component for heart rates up toabout 220 bpm. Other high frequency cut offs may be used for othercardiac rates. Processing the thoracic impedance signal using signalprocessing characteristics suitable for respiration sensing produces asignal that is under-sampled and over-filtered for detecting the alteredrespiratory state during phrenic nerve activation.

Graph 1320 represents a thoracic impedance signal processed to obtainthe higher frequency deflections 1301, 1302, 1303, 1304 in the impedancesignal caused by phrenic nerve activations. The signal illustrated ingraph 1320 is digitized by sampling at a higher rate than that used forgraph 1310, e.g., about 100 Hz, to allow reconstruction of the higherfrequencies. The high frequency cutoff of the filtering used to acquiregraph 1320 is extended beyond that used to obtain graph 1310, so thatthe higher frequency phrenic nerve activation components are notsubstantially attenuated. Additionally, one or more notch filters may beused to attenuate the cardiac component and/or other noise frequenciesfrom the sensor signal. The notch filter may be adaptable based oncardiac rate. In various implementations, the notch filter may attenuatefrequencies in the range of about 0.5 to about 4 Hz. For example, notchfiltering in the range of about 0.5 Hz to about 1.5 Hz may be used toattenuate the cardiac component for a cardiac rate of about 90 bpm. Anupper notch frequency of about 4 Hz may be used to attenuate the cardiaccomponent for a cardiac rate of about 220 bpm.

The signal represented by graph 1320 could be used for both respirationsensing and phrenic nerve activation sensing. However, it can beappreciated that the deflections 1301, 1302, 1303, 1304 caused byphrenic nerve activation superimposed on the respiration signal may bedifficult to discern and that additional filtering could enhance thesignal for phrenic nerve activation detection.

Using a high pass filter, the respiration and cardiac components of theMV signal can be substantially removed, as illustrated in graph 1330. Inone example, filtering for phrenic nerve activation sensing may involvethe use of a filter having a low frequency cut off of about 5 Hz and ahigh frequency cut off of about 20 Hz. This filtering implementationsubstantially attenuates low frequency noise, the respiration component,and the cardiac component from the thoracic impedance signal, whileretaining frequencies indicative of the phrenic nerve activations 1301,1302, 1303, 1304.

Returning now to FIG. 11A, the output 1112 of the first signalprocessing circuitry 1111 may comprise an activity or metabolic demandsignal which is optimally filtered for that purpose and is used by rateadaptive pacing control circuitry 1115 to determine a sensor indicatedrate (SIR) 1117. The output 1112 of the first signal processingcircuitry 1111, e.g., respiration signal or patient activity signal,etc., may also be used to track the parameters sensed directly using thesensor or derived from the sensor signal for diagnostic or otherpurposes.

The output 1122 from the second signal processing circuitry 1121 isoptimally filtered for detection of phrenic nerve activation asdescribed, for example, in connection with FIGS. 12 and 13. The output1122 is coupled to phrenic nerve activation detection circuitry 1125.The phrenic nerve activation detection circuitry 1125 analyzes thesignal 1122 and provides an output 1127 indicating the presence orabsence of phrenic nerve activation. The output 1127 from the phrenicnerve activation detection circuitry can be used in conjunction with acardiac capture threshold test to determine a cardiac pacing thresholdor pacing output configuration that avoids phrenic nerve activation.

The filters used in the first signal processing circuitry 1111 and thefilters used in the second signal processing circuitry 1121 may be ofany suitable type, including any combination of high pass, low pass,band pass, and/or notch filters. In some implementations, for example, anumber of filters may be arranged in series. The filters may use varioustechnology implementations including any combination of analog and/or,digital filters, e.g., 1^(st), 2^(nd), or Nth-order filters,non-recursive (finite impulse response (FIR)), recursive (infinite inputresponse (IIR)), Chebyshev, Bessel, Butterworth, etc.

Some embodiments use filter circuitry in the second signal processingcircuitry 1121 that is matched to the analog front-end filter circuitry,which may be implemented in the pre-processing circuitry 1109. Since thediaphragmatic “hiccup” caused by phrenic nerve activation resembles animpulse function, the resultant sensor signal 1107 after the analogfiltering is applied in the pre-processing circuitry will be close tothe impulse response of the pre-processing analog filtering. The filtercircuitry in the second signal processing circuitry 1121 may include afilter with characteristics matched to the impulse response of theanalog filtering of the pre-processing circuitry 1109. The matchedfilter would pass phrenic nerve activation signals and substantiallyreject non-phrenic nerve activation signals, including non-impulseresponses along with low frequency noise. In some implementations, thecharacteristics of the matched filter would be predesignated based onthe design of the system. In some implementations, the characteristicsof the matched filter could be individually mapped based on an exampleimpulse response during device testing.

In some embodiments, the medical device does not have physicallyseparate channels for processing the sensor signal for detecting therate adaptation parameter and processing the sensor signal for phrenicnerve activation detection. In these embodiments, as illustrated by FIG.11B, a single signal processing channel 1130, including signalprocessing circuitry 1131 is used to implement time-multiplexed signalprocessing functions. The signal processing circuitry 1131 may includean A/D converter, filters, amplifiers, etc. The single channel 1130 isprogrammable to apply different signal processing characteristics to thesensor signal 1107 during different time periods. The output 1139 of thesignal processing circuitry 1131 is a data stream that includes a firstportion of the signal 1132 that is optimal for phrenic nerve activationdetection during time interval, T₁, and includes a second portion of thesignal 1133 that is optimal for activity/metabolic demand sensing forrate-adaptive pacing during a second time period, T₂. A first set ofsignal processing characteristics (A/D conversion characteristics,amplifier characteristics, filter characteristics, etc.) is applied bythe signal processing circuitry 1131 to the sensor signal 1107 toproduce the portion of the signal 1132 tailored for phrenic nerveactivation detection which is output during T₁. A second set of signalprocessing characteristics is applied by the signal processing circuitry1131 to the sensor signal 1107 to produce the portion of the signal 1133tailored for activity/metabolic demand sensing for rate-adaptive pacingand/or other functions during T2.

The embodiment of 11B reduces the circuitry required to apply differentsignal processing characteristics for activity/metabolic demanddetermination and phrenic nerve activation detection. The phrenic nerveactivation detection functionality may be unused other than during acardiac capture threshold test and/or during periods wherein sensing forphrenic nerve activation is desirable.

The use of both an activity sensor (e.g., accelerometer) and a metabolicdemand sensor (e.g., MV sensor) for rate-adaptive pacing has been usedto exploit the strengths of both sensor types and achieve a morephysiologic adaptation of pacing rate. In some configurations, theoutputs of an accelerometer and an MV sensor are blended such that theaccelerometer is used during an initial phase of rate adaptation and theMV sensor is used during a second phase of rate adaptation. For example,the accelerometer output alone may be initially used to adapt the pacingrate, with the influence of the accelerometer output decreasing withtime as the output of the MV sensor becomes more predominantly used forrate adaptation.

Medical devices that use blended sensor outputs for rate adaptation areillustrated in FIGS. 14A-C. The illustrated devices include anaccelerometer 1401 and an MV sensor 1402. The outputs from theaccelerometer 1401 and the MV sensor 1402 are processed by first signalconditioning channels 1410, 1440 having circuitry 1411, 1441 designedfor activity sensing and respiration sensing, respectively. The outputof the first accelerometer signal processing circuitry 1412 and theoutput of the first impedance signal processing circuitry 1442 are usedby rate-adaptive pacing control circuitry 1450 to develop a sensorindicated rate signal 1451.

One or both of the accelerometer signal 1403 and the impedance sensorsignal 1404 may additionally be processed using a separate channel 1430,1420 having circuitry 1431, 1421 designed for enhanced detection ofphrenic nerve activation. The signal output(s) 1432, 1422 of the secondsignal processing circuitry 1431, 1421, are used by the phrenic nerveactivation detection circuitry 1460 to detect phrenic nerve activation.Based on one or both signals 1432, 1422, the phrenic nerve activationcircuitry 1460 outputs a signal 1461 indicative of phrenic nerveactivation (PNA).

FIG. 14C illustrates a medical device that detects phrenic nerveactivation based on signal deflections caused by phrenic nerveactivation in the signal output 1432 from the second accelerometersignal processing circuitry 1431. FIG. 14B illustrates a medical devicethat detects phrenic nerve activation based on signal deflections causedby phrenic nerve activation in the signal output 1422 from the secondimpedance signal processing circuitry 1421.

FIG. 14A illustrates a medical device that detects phrenic nerveactivation based on both the output 1432 of the second accelerometersignal processing circuitry 1431 and the output 1422 of the secondimpedance signal processing circuitry 1421. Using both outputs 1432,1422 to detect phrenic nerve activation may involve, for example,comparing each output 1432, 1422, respectively, to a threshold anddetecting phrenic nerve activation based on the comparison of bothsignals 1432, 1422 to their respective thresholds. In someimplementations, the signal 1432, 1422 derived from one sensor, e.g.,accelerometer 1401, thoracic impedance 1402, may be used to initiallydetect phrenic nerve activation, and the signal 1422, 1432 derived fromthe other sensor, e.g., thoracic impedance 1402, 1401, accelerometer,may be used to confirm the initial detection of phrenic nerveactivation.

As previously discussed above, the threshold for phrenic nerveactivation may be lower during certain phases of the respiration cyclemaking phrenic nerve activation more prevalent during these respirationcycle phases. In these situations, phrenic nerve activation detectionmay be enhanced by taking into account the phase of the respirationcycle. As indicated in FIGS. 14A-C, the signal output 1442 from thefirst impedance signal processing circuitry, which is designed forsensing respiration cycles, may be used by the phrenic nerve activationdetection circuitry 1460 to detect phrenic nerve activation based onrespiration cycle phase.

The flow diagram of FIG. 15 illustrates processes implementable in a CRMdevice for detecting phrenic nerve activation. FIG. 15 illustrates animplementation for PNA detection based on acquiring 1510 a sensor signalwhich is modulated by a physiological parameter modulated by hemodynamicrequirements of the patient, e.g., activity or MV. The sensor signal isprocessed 1515 using a first channel having a first set of signalprocessing characteristics to develop a rate-adaptation signal. Thesensor signal is processed 1520 using a second channel having a secondset of signal processing characteristics to develop a phrenic nerveactivation signal. After delivery 1525 of a pacing pulse to a cardiacchamber, a PNA detection interval is initiated 1530. The PNA detectioninterval may extend for 500 ms, ending before the next pacing pulse tothe cardiac chamber is delivered. The device senses 1535 for anindication of PNA in the PNA signal during the PNA detection interval.If PNA is not detected 1540, pacing continues. However, if PNA isdetected 1540, the pacing output configuration may be altered 1545 toreduce PNA, or other action may be taken.

The medical devices and processes illustrated in any of FIGS. 11 and 15can be implemented in the CRM device of FIG. 10 and can be used inconjunction with determination of phrenic nerve activation based onrespiration phase, as illustrated, for example, in FIGS. 1-9. Theapproaches outlined by the flow diagrams of FIGS. 1 and 6 may use theenhanced signal processing for the phrenic nerve activation signal asdescribed herein. These techniques are particularly useful for leftventricular (LV) capture threshold determination since the position ofthe LV electrodes is more likely to cause phrenic nerve activation.

Although some implementations previously described use an accelerometersignal for phrenic nerve activation detection based on respirationphase, it will be appreciated after reading this disclosure that similartechniques may also be implemented using a phrenic nerve activationsignal derived from the thoracic impedance signal. The use of a thoracicimpedance sensor for PNA detection may be advantageous in somesituations because only one sensor is required to develop therespiration signal, determine a SIR for rate adaptive pacing, and detectphrenic nerve activation based on respiration phase.

The flow diagram of FIG. 16 illustrates various optional processes 1610that may be used in connection with detection of phrenic nerveactivation. In this example, a thoracic impedance signal and/or anaccelerometer signal are acquired 1620. The thoracic impedance signal isprocessed 1630 using first signal processing characteristics to developa respiration signal. Optionally, the thoracic impedance signal may beprocessed using second signal processing characteristics to develop aphrenic nerve activation signal. If an accelerometer signal is used, theaccelerometer signal may be processed 1640 using first signal processingcharacteristics to develop a patent activity signal, for example. Theaccelerometer signal may alternatively or additionally be processedusing second signal processing characteristics to develop a phrenicnerve activation signal.

The respiration phase is determined 1650 using the respiration signal,which in this example is developed from the thoracic impedance signal,but in other implementations may be developed using sensors other than athoracic impedance sensor. A cardiac pacing pulse is delivered 1660during the respiration phase. The algorithm determines 1670 whether thephrenic nerve was stimulated by the pacing pulse during the respirationphase using one or both of the phrenic nerve activation signal developedfrom the thoracic impedance signal and the phrenic nerve activationsignal developed from the accelerometer.

FIGS. 17A-B depict a flow diagram illustrating an algorithm for capturethreshold testing that also includes a process for ensuring that thepacing voltage does not produce phrenic nerve activation. The patient'sthoracic impedance signal is acquired 1702 by a CRM device. The thoracicimpedance signal may be processed using 1703 first thoracic impedancesignal processing characteristics to develop the respiration signal.Optionally, the thoracic impedance signal may also be processed using1704 second thoracic impedance signal processing characteristics todevelop a phrenic nerve activation signal.

A signal is acquired 1706 from an accelerometer. The accelerometersignal may be processed using 1707 first accelerometer signal processingcharacteristics to produce a respiration signal. Alternately oradditionally, the accelerometer signal may be processed using 1708second accelerometer signal processing characteristics to produce aphrenic activation signal.

Normal pacing may involve rate adaptation based on patient activityand/or metabolic need. A sensor indicated rate (SIR) is determined 1710based on one or both of the respiration signal and the patent activitysignal. The SIR is used to adjust 1712 pacing rate based on patientactivity and/or metabolic need.

At periodic intervals, on command, or triggered by sensed events,cardiac capture threshold testing is initiated 1714. A cardiac capturethreshold test may implement a step-down threshold search, a step-upthreshold search, or may use binomial or other search patterns. In theexample of FIG. 17A, a step-down search is illustrated. The test pacingvoltage is decremented 1718 until loss of capture (LOC) is detected1720. The pacing voltage just above the test voltage at which LOC isdetected is identified 1722 as the cardiac capture threshold for theparticular pacing electrode combination under test.

In a process such as the one illustrated in FIG. 7, the transition zonefor the electrode configuration is determined 1724. The phrenic nerveactivation signal(s) used in determining the transition zone may be oneor both of the PNA signal developed using the accelerometer as in block1708 and the PNA signal developed using the thoracic impedance signal asin block 1704. After the cardiac capture threshold is identified, thealgorithm checks 1726 to determine the relationship of the pacingvoltage (the cardiac capture threshold plus a safety margin) to thetransition zone. In one implementation, if pacing voltage is below thelower boundary of the transition zone, then the pacing voltage is usedfor pacing. If the pacing voltage is above the lower boundary of thetransition zone, then the algorithm may continue searching for anacceptable pacing output configuration by changing a pacing outputconfiguration parameter such as the pulse width or electrodecombination, for example. Some implementations may not require that thepacing voltage be below the transition zone boundary and may use thepacing voltage if the pacing voltage falls within a lower portion thetransition zone.

The components, functionality, and structural configurations depictedherein are intended to provide an understanding of various features andcombination of features that may be incorporated in an implantablepacemaker/defibrillator. It is understood that a wide variety of cardiacmonitoring and/or stimulation device configurations are contemplated,ranging from relatively sophisticated to relatively simple designs. Assuch, particular cardiac device configurations may include particularfeatures as described herein, while other such device configurations mayexclude particular features described herein.

Various modifications and additions can be made to the preferredembodiments discussed hereinabove without departing from the scope ofthe present invention. Accordingly, the scope of the present inventionshould not be limited by the particular embodiments described above, butshould be defined only by the claims set forth below and equivalentsthereof.

We claim:
 1. An implantable medical device, comprising: a pulsegenerator configured to deliver cardiac pacing to a heart; a singleimpedance sensor configured to generate a signal modulated by patientrespiration, the sensor signal available at a sensor output terminal; afirst filter channel coupled to the sensor output terminal, the firstfilter channel configured to attenuate first frequencies of the sensorsignal to produce a first filtered output; a second filter channel,separate from the first filter channel, coupled to the same sensoroutput terminal, the second filter channel configured to attenuatesecond frequencies of the sensor signal to produce a second filteredoutput; and circuitry configured to evaluate patient respiration usingthe first filtered output and to detect phrenic nerve activation causedby cardiac pacing using the second filtered output.
 2. The device ofclaim 1, wherein the second filtered output substantially comprisesphrenic activation signal components and does not substantially includerespiration signal components.
 3. The device of claim 1, wherein secondfilter channel comprises a filter having one or more cut off frequenciesthat are dynamically alterable.
 4. The device of claim 1, wherein secondfilter channel comprises a high pass filter having a low frequency cutoff of about 5 Hz.
 5. The device of claim 1, further comprising analogcircuitry coupled between the sensor output and the first and secondfilter channels, wherein the second filter channel includes a filtercircuit that is substantially matched to an impulse response of theanalog circuitry.
 6. The device of claim 5, wherein the filter circuitsubstantially attenuates frequencies other than the impulse responsefrequencies of the analog circuitry.
 7. The device of claim 5, whereinthe filter circuitry is individually mapped to the impulse responseduring device testing.
 8. The device of claim 1, wherein the circuitryincludes a timer configured to time a phrenic nerve activation detectioninterval which is started following delivery of a pacing pulse to acardiac chamber and is stopped before delivery of a subsequent pacingpulse to the cardiac chamber and the circuitry is configured to sensefor phrenic nerve activation during the phrenic nerve detectioninterval.
 9. The device of claim 1, further comprising pacing controlcircuitry configured to adapt a cardiac pacing rate based on evaluationof the patient respiration.
 10. The device of claim 1, furthercomprising a second sensor configured to produce a sensor signal,wherein the circuitry is configured to use both the sensor signal andthe second filtered output to detect the phrenic nerve activation. 11.The device of claim 1, further comprising: an accelerometer configuredto generate a signal modulated by acceleration that is available at anaccelerometer output terminal; a third filter channel coupled to theaccelerometer output terminal, the third filter channel configured toattenuate third frequencies of the accelerometer signal to produce athird filtered output; and a fourth filter channel coupled to theaccelerometer output, separate from the third filter channel, the fourthfilter channel configured to attenuate fourth frequencies of theaccelerometer signal to produce a fourth filtered output, wherein thecircuitry is configured to detect the phrenic nerve activation using thesecond filtered output and the fourth filtered output.
 12. The device ifclaim 1, wherein the circuitry is configured to develop a sensorindicated pacing rate based on one or both of the first filtered outputand the third filtered output.
 13. The device of claim 1, wherein thecircuitry is configured to use the first filtered output to determinerespiration phase and is configured to use the second filtered output todetect the phrenic nerve activation in conjunction with the respirationphase.
 14. A method of operating an implantable medical device,comprising: sensing patient respiration and generating a single sensorsignal modulated by patient respiration at a sensor output terminal;processing the single sensor signal through separate signal processingchannels, the separate signal processing channels comprising a firstsignal processing channel having first signal processing characteristicsand a second signal processing channel having second signal processingcharacteristics; evaluating patient respiration using an output of thefirst signal processing channel; and detecting phrenic nerve activationcaused by cardiac pacing using an output of the second signal processingchannel.
 15. The method of claim 14, wherein: the first signalprocessing channel comprises first filter circuitry and the first signalprocessing characteristics are configured to attenuate a first set offrequencies from the sensor signal; and the second signal processingchannel comprises a second filter circuitry and the second signalprocessing characteristics are configured to attenuate a second set offrequencies from the sensor signal.
 16. The method of claim 14, whereinthe second signal processing channel comprises a notch filter havingcharacteristics that are adaptable based on cardiac rate.
 17. The methodof claim 14, wherein the second signal processing characteristicscomprise a low frequency cut off that substantially attenuatesrespiration components and cardiac components from the output of thesecond signal processing channel.
 18. The method of claim 14, whereindetecting the phrenic nerve activation comprises: starting a phrenicnerve activation detection interval upon or after delivery of a cardiacpace during a cardiac cycle; ending the phrenic nerve activationdetection interval during the cardiac cycle; and sensing for the phrenicnerve activation during the phrenic nerve detection interval.
 19. Themethod of claim 14, further comprising: determining a transition zonefor phrenic nerve activation; determining a cardiac capture threshold;and setting a cardiac pacing energy above the cardiac capture thresholdand below a transition zone threshold for phrenic nerve activation. 20.The method of claim 14, further comprising switching from one cardiacpacing electrode configuration to another cardiac pacing electrodeconfiguration based on detection of the phrenic nerve stimulation.